1. Field of the Invention
The present invention is generally directed to a substrate used for tissue engineering. The substrate is a biodegradable elastomeric polymer. Methods and compositions for testing and using the same are disclosed.
2. Background of the Related Art
The field of tissue engineering has slowly emerged within the past 2 decades, driven primarily by the large demand for replacement of diseased or damaged tissue [1]. Tissue engineering presents enormous challenges and opportunities for materials science from the perspective of both materials design and materials processing [2]. Successful tissue regeneration must go beyond reproducing shape and structure to restore biological and mechanical function and long-term integration with surround native tissues [3]. Tissue engineering requires the use of a three dimensional scaffold for cells to grow and differentiate properly.
Generally, the ideal cell scaffold in tissue engineering should be biocompatible and biodegradable, promote cellular interaction and tissue development, and possess proper mechanical and physical properties. The cell scaffolds are implanted in a mechanically dynamic environment in the body; the scaffold must sustain and recover from various deformations without mechanical irritations to the surrounding tissues. The properties of scaffolds should resemble those of the extracellular matrix (ECM), a soft, tough, and elastomeric proteinaceous network that provides mechanical stability and structural integrity to tissues and organs [4].
Mechanical stimuli play an important role in the development of tissues. In vascular engineering, for example, the extent to which the initial compliance may affect the long-term function of the graft remains controversial [5]. It has long been realized the fibrous tissue formation within and surrounding and implanted vascular graft would compromise graft compliance. Compliance mismatch between the grafts and host vessel may contribute to the development of incomplete endothelialization and myointimal hyperplasia at the anastomotic regions. Hence, elastomeric materials are attractive in tissue engineering especially in soft tissue engineering such as vascular, ligament, and meniscus engineering [6].
Current elastomers in tissue engineering can be categorized as naturally derived materials and synthetic polymers. Naturally derived materials such as collagen and elastin must be isolated from human, animal or plant tissue. This process typically results in a high cost and large batch to batch variations. These materials also exhibit a limited range of physical properties and immune response is always a concern [7][8]. Typical synthetic elastomeric materials include poly(4-hydroxybutyrate) (P4HB), polyurethane (PU), polycarpolactone (PCL), poly(glycerol-sebacate) (PGS) [4] and so on. PHB has a much higher modulus (stiffer) and much lower sfum to failure compared the normal soft tissues. PU has been investigated extensively as elastomeric materials for vascular grafts. One major concern about PU, however, is the potential carcinogenic effect of its degradation products. A statement issued by FDA suggested that the implanted PU foam might degrade and form 2,4-toluene diamine, which has been shown to cause liver cancer in laboratory animals [6]. PCL is a semi-crystalline linear resorbable aliphatic elastomeric polyester.
The Food and Drug Administration (FDA) has approved a number of medical and drug delivery devices made by PCL. However, applications of PCL might be limited because degradation and resorption of PCL are considerably slow due to its hydrophobic character and high crystallinity. The hydrophobic surface also has impacts to the cell attachment on PCL [9]. PGS is a newly developed elastomer which exhibits good mechanical properties and biocompatibility. High temperature and high vacuum, however, are needed for the polymer synthesis. [10]